Scutellarin protects against the liver injury induced by diosbulbin B in mice and its mechanism. (22nd April 2015)

• Record Type: Journal Article
• Authors: Niu, Chengwei; Sheng, Yuchen; Yang, Rui; Lu, Bin; Bai, Qingyun; Ji, Lili; Wang, Zhengtao
• Is Part Of: Journal of ethnopharmacology. Volume 164(2015)
• Page Start: 301
• Page End: 308
• Publication Date: 2015-04-22
• Subjects: DB diosbulbin B -- SC scutellarin -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- ALP alkaline phosphatase -- MPO myeloperoxidase -- TNF-α tumor necrosis factor alpha -- IL-6 interleukin 6 -- IFN-γ interferon-γ -- IκB inhibitor of kappa B -- NF-κB nuclear factor κB -- MDA malondialdehyde -- GSH glutathione -- GPx glutathione peroxidase -- DTNB 5, 5׳-Dithio-bis(2-nitrobenzoic acid) -- ELISA enzyme-linked immunosorbent assay -- H&E hematoxylin–eosin -- LPO lipid peroxidation -- EF ethyl acetate fraction of Dioscorea bulbifera -- SE ethanol extract of Scutellaria barbata; Diosbulbin B -- Scutellarin -- Hepatotoxicity -- Inflammation -- Oxidative stress injury -- Anti-tumor; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2015.02.031
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Diosbulbin B (DB) is the main hepatotoxic compound distributed in Dioscorea bulbifera L., which is widely used for the treatment of cancer and thyroid disorders in Asia. Scutellarin (SC) is the main compound in medicinal herb Scutellaria barbata D. Don, which is usually combined with Dioscorea bulbifera used for cancer therapy in clinic. Aim of the study: This study aims to investigate the protection of SC against the liver injury induced by DB and its engaged mechanism. In addition, the anti-tumor effect of DB and SC is further observed in vivo . Materials and methods: The protection of SC against DB-induced liver injury was evaluated by detecting serum alanine/aspartate aminotransferases (ALT/AST) and alkaline phosphatase (ALP) activities, and further liver histological observation. The inflammatory response was assessed by detecting liver myeloperoxidase (MPO) activity, and serum levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon-γ (IFN-γ). Western-blot analysis was used to detect the protein expression. The oxidative liver injury was evaluated by detecting liver malondialdehyde (MDA) and glutathione (GSH) contents, and glutathione peroxidase (GPx) enzymatic activity. In vivo anti-tumor activity was analyzed in S180 tumor-bearing mice. Results: SC significantly decreased the increased serum ALT/AST, and ALP activities induced by DB. Liver histological observation evidenced the protection of SC against DB-induced liver injury. SC obviously reduced the increased liver MPO activity and the number of MPO-positive staining cells induced by DB. SC also reversed the decreased expression of inhibitor of κB (IκB) and the translocation of nuclear factor κB (NF-κB) p65 from cytoplasm to nucleus induced by DB. In addition, SC significantly abrogated the increased serum levels of TNF-α, IL-6, and IFN-γ induced by DB. SC decreased the increased liver MDA content induced by DB significantly, and it also increased liver GSH level. The decreased GPx protein expression and its enzymatic activity induced by DB were both obviously reversed after SC treatment. The results in S180 tumor-bearing mice showed that SC combined with DB significantly inhibited tumor growth in vivo . Conclusions: Our results demonstrate that SC prevents DB-induced liver injury by attenuating NF-κB-mediated hepatic inflammation and ameliorating liver oxidative stress injury. Meanwhile, DB plus SC has significant anti-tumor activity in vivo . This study indicates the potential combination of DB with SC for the treatment of cancer in clinic. Graphical abstract: